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Development of Alzheimer's disease associated with loss of body mass

A research found that loss of body mass over time appears to be strongly linked to older adults' risk of developing Alzheimer's disease ( AD ), and the greater the loss the greater the chance of a person developing the disease.

The findings are the first to associate decline in body mass index ( BMI ) with the eventual onset of Alzheimer's disease.
The researchers suggest that the loss of body mass reflects disease processes and that change in BMI might be a clinical predictor of the development of Alzheimer's disease.

The research, reported in the Neurology, was conducted by Aron S. Buchman, David A. Bennett, and colleagues at Rush University Medical Center in Chicago, IL, as part of the Religious Orders Study.

" People with Alzheimer's disease are known to lose weight and body mass after they have the disease," says Dallas W. Anderson, program director for population studies in the Dementias of Aging Branch of NIA's Neuroscience and Neuropsychology of Aging Program. " This study is significant in that it looks at body mass changes in the years preceding dementia and cognitive decline. Other studies have looked at BMI at only one point in time or studied body mass loss in people who already have Alzheimer's disease."

Each of the 820 study participants took part in yearly clinical evaluations that included a medical history, neurologic examination, and extensive cognitive function testing.
The participants' weights and heights were also measured to determine their BMI, a widely used measure of body composition that is calculated by dividing weight in kilograms by height in meters squared.
They completed an average of 6.6 annual evaluations, with a 95 percent follow-up rate. All of the participants were older than 65 years, and the vast majority of them were white and of European ancestry.

When the study began, none of the participants had dementia, and their average BMI was 27.4. During the follow-up period, 151 of the participants ( 18.4 percent ) developed Alzheimer's disease. Both baseline BMI and the annual rate of change in BMI were linked to the risk of developing AD.

People who lost approximately one unit of BMI per year had a 35 percent greater risk of developing Alzheimer's disease than that of people with no change in BMI over the course of the study.
Those with no change in BMI had a 20 percent greater risk of developing the disease than that of people who gained six-tenths of a unit of BMI per year.

The findings held true even after adjusting for factors such as chronic health problems, age, sex, and education. They also held true when those who developed Alzheimer's disease in the first 4 years of follow-up--and might have had mild, undiagnosed AD early in the study--were excluded from the analysis.

The investigators found a similar relationship between changes in BMI and rate of cognitive decline, which is the clinical hallmark of Alzheimer's disease.
Even when controlling for baseline cognitive function, baseline BMI, age, sex, and education, the rate of cognitive decline among people losing approximately one unit of BMI per year was more than 35 percent higher than that of people with no change in BMI and 80 percent higher than that of people who gained six-tenths of a unit of BMI per year.

Further analyses showed that depressive symptoms, participants' physical activity levels, and female participants' use of estrogen replacement did not explain the link between BMI loss and development of Alzheimer's disease.

In addition, when the researchers looked at changes in weight rather than BMI, they found that a loss of 1 pound per year was associated with a 5 percent increase in the risk of Alzheimer's disease.

" These findings suggest that subtle, unexplained body mass and weight loss in an older person may be an early sign of Alzheimer's disease and can precede the development of obvious memory problems," explains Bennett, who directs the Rush Alzheimer's Disease Center. " The most likely explanation is that there is something about these individuals or about this disease that affects BMI before the clinical syndrome becomes apparent--that loss of BMI reflects the disease process itself."

" Our understanding of Alzheimer's disease is changing as we get more information, particularly as we look at the pathology of the disease," adds Buchman, the lead investigator for the study. "It turns out that Alzheimer's disease not only results in cognitive dysfunction, but also may have a variety of other symptoms, depending on which brain regions are affected. If the disease pathology affects a region of the brain that controls weight, your body mass may decline prior to loss of cognition."

" There are actually very few predictors of Alzheimer's disease," Bennett explains. " This study makes us think about the spectrum of clinical signs of AD beyond changes in memory and behavior and motor skills. Changes in BMI are easy to measure in a doctor's office without an expensive scan," he says.